کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9891500 1540762 2005 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
SC-435, an ileal apical sodium-codependent bile acid transporter inhibitor alters mRNA levels and enzyme activities of selected genes involved in hepatic cholesterol and lipoprotein metabolism in guinea pigs
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
SC-435, an ileal apical sodium-codependent bile acid transporter inhibitor alters mRNA levels and enzyme activities of selected genes involved in hepatic cholesterol and lipoprotein metabolism in guinea pigs
چکیده انگلیسی
We have demonstrated that SC-435, an apical sodium codependent bile acid transporter (ASBT) inhibitor, lowers plasma low-density lipoprotein cholesterol (LDL-C) concentrations in guinea pigs. The purpose of this study was to further examine the hypocholesterolemic effects of SC-435, by measuring the activity and RNA expression of regulatory enzymes of hepatic cholesterol and lipoprotein metabolism. In addition, the use of a combination (COMBO) therapy with simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, was also tested. Male Hartley guinea pigs were randomly allocated to one of three diets (n=10 per group), for 12 weeks. The control diet contained no ASBT inhibitor or simvastatin. The monotherapy diet (ASBTi) contained 0.1% of SC-435. The COMBO therapy consisted of a lower dose of SC-435 (0.03%) and 0.05% simvastatin. Cholesterol ester transfer protein (CETP) and HMG-CoA reductase mRNA abundance were determined using RT-PCR techniques. Hepatic HMG-CoA reductase and cholesterol 7α-hydroxylase (CYP7) activities were measured by radioisotopic methods. Compared to the control group, CETP activity was 34% and 56% lower with ASBTi and COMBO, respectively. Similarly, CETP mRNA expression was reduced by 36% and 73% in ASBTi and COMBO groups, respectively. Cholesterol 7α-hydroxylase and HMG-CoA reductase activities were increased ∼2-fold with ASBTi and COMBO treatments, respectively. Likewise, HMG-CoA reductase mRNA expression was increased 33% with ASBTi treatment. These results suggest that both SC-435 monotherapy and combination therapy lower LDL cholesterol concentrations by altering both hepatic cholesterol homeostasis and the intravascular processing of lipoproteins in guinea pigs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Nutritional Biochemistry - Volume 16, Issue 12, December 2005, Pages 722-728
نویسندگان
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